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Apoptotic effect of eugenol envolves G2/M phase abrogation accompanied by mitochondrial damage and clastogenic effect
Paulo Luiz de Sá Júnior1, Diana Aparecida Dias Câmara2, André Santos Costa3
1Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil, .
Background:
Eugenol (EUG) is a major phenolic compound present in clove whose anti-cancer properties have been demonstrated previously. These anti-cancer properties may involves the modulation of different mechanisms, including α-estrogen receptor (αER) in luminal breast cancer cells, COX-2 inhibition in melanoma cells or p53 and caspase-3 activation in colon cancer cells.
Hypothesis:
EUG promotes a burst in ROS production causing cell-cycle perturbations, mitochondria toxicity and clastogenesis triggering apoptosis in melanoma breast- and cervix-cancer cells in vitro.
Methods:
Morphological changes were evaluated through the light- and electronic- microscopy. Cell-cycle, ROS, PCNA and Apoptosis was detected by flow cytometry and clastogenicity was evaluated by Comet-assay.
Results:
The results obtained herein pointed out that EUG promotes, increasing ROS production leading to abrogation of G2/M of phase of cell-cycle, and consecutively, clastogenesis in vitro. In addition, EUG induces Proliferation Cell Nuclear Antigen (PCNA) downregulation and decreasing in mitochondria potential (ΔΨm). Of note, a Bax up-regulation was also observed on cells treated with EUG. All of these findings cooperate in order to induce apoptosis in cancer cells.
Conclusion:
These promising results presented herein shed new light on the mechanisms of action of EUG suggesting a possible applicability of this phenylpropanoid as adjuvant in anti-cancer therapy.
Insights
Eugenol (EUG), a compound from cloves, triggers cancer cell death by increasing reactive oxygen species (ROS) and damaging DNA. This natural compound shows promise as an adjuvant in cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Eugenol (EUG) is a phenolic compound from cloves with demonstrated anti-cancer properties.
- Potential mechanisms include modulating alpha-estrogen receptor (αER), COX-2 inhibition, and activating p53/caspase-3.
- EUG's anti-cancer effects are linked to reactive oxygen species (ROS) production, cell-cycle disruption, and apoptosis induction.
Purpose of the Study:
- To investigate the in vitro mechanisms by which Eugenol (EUG) induces apoptosis in cancer cells.
- To elucidate EUG's effects on cell cycle, ROS production, mitochondrial potential, and DNA integrity.
Main Methods:
- Morphological analysis using light and electron microscopy.
- Flow cytometry for cell-cycle, ROS, Proliferation Cell Nuclear Antigen (PCNA), and apoptosis assays.
- Comet assay to evaluate clastogenicity (DNA damage).
Main Results:
- EUG significantly increases ROS production, leading to G2/M cell-cycle arrest and clastogenesis.
- Downregulation of PCNA and decreased mitochondrial membrane potential (ΔΨm) were observed.
- Upregulation of Bax and induction of apoptosis were confirmed in EUG-treated cancer cells.
Conclusions:
- EUG induces cancer cell apoptosis through ROS generation, cell-cycle arrest, and DNA damage.
- The findings highlight EUG's potential as an adjuvant in anti-cancer therapy.
- Further research into EUG's therapeutic applications is warranted.
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